2. Core Curriculum Contents Introduction Transmission and Pathogenesis Epidemiology of TB in the U.S. Testing for TB Disease and Infection Diagnosis of TB Treatment of Latent TB Infection (LTBI) Treatment of TB Disease Infection Control in Health Care Settings BCG Vaccination Community TB Control

3. Introduction

4. Areas of Concern TB cases continue to be reported in every state Drug-resistant cases reported in almost every state Estimated 10-15 million persons in U.S. infected with M. tuberculosis - Without intervention, about 10% will develop TB disease at some point in life

5. Transmission and Pathogenesis

6. Transmission of M. tuberculosis Spread by droplet nuclei Expelled when person with infectious TB coughs, sneezes, speaks, or sings Close contacts at highest risk of becoming infected Transmission occurs from person with infectious TB disease (not latent TB infection)

7. Probability TB Will Be Transmitted Infectiousness of person with TB Environment in which exposure occurred Duration of exposure Virulence of the organism

8. Pathogenesis 10% of infected persons with normal immune systems develop TB at some point in life HIV strongest risk factor for development of TB if infected - Risk of developing TB disease 7% to 10% each year Certain medical conditions increase risk that TB infection will progress to TB disease

9. Conditions That Increase the Risk of Progression to TB Disease HIV infection Substance abuse Recent infection Chest radiograph findings suggestive of previous TB Diabetes mellitus Silicosis Prolonged corticosteriod therapy Other immunosuppressive therapy

10. Conditions That Increase the Risk of Progression to TB Disease (cont.) Cancer of the head and neck Hematologic and reticuloendothelial diseases End-stage renal disease Intestinal bypass or gastrectomy Chronic malabsorption syndromes Low body weight (10% or more below the ideal)

11. Common Sites of TB Disease Lungs Pleura Central nervous system Lymphatic system Genitourinary systems Bones and joints Disseminated (miliary TB)

12. Drug-Resistant TB Drug-resistant TB transmitted same way as drug-susceptible TB Drug resistance is divided into two types: - Primary resistance develops in persons initially infected with resistant organisms - Secondary resistance (acquired resistance) develops during TB therapy

13. Classification System for TB No TB exposure Not infected No history of exposure Negative reaction to tuberculin skin test TB exposure No evidence of infection History of exposure Negative reaction to tuberculin skin test TB infection No disease Positive reaction to tuberculin skin test Negative bacteriologic studies (if done) No clinical, bacteriological, or radiographic evidence of active TB TB, clinically activeM. tuberculosis cultured (if done) Clinical, bacteriological, or radiographic evidence of current disease TB Not clinically active History of episode(s) of TB or Abnormal but stable radiographic findings Positive reaction to the tuberculin skin test Negative bacteriologic studies (if done) and No clinical or radiographic evidence of current disease TB suspected Diagnosis pending Class Type Description 0 1 2 3 4 5

15. TB Morbidity Trends in the United States From 1953 to 1984, reported cases decreased by an average of 5.6% per year From 1985 to 1992, reported TB cases increased by 20% Since 1993, reported TB cases have been declining again 18,361 cases reported in 1998

16. Reported TB Cases United States, 1953 - 1998 Year 10,000 20,000 * * 30,000 50,000 70,000 100,000 Cases (Log Scale) *Change in case definition 536070809098

17. Factors Contributing to the Increase in TB Morbidity: 1985-1992 Deterioration of the TB public health infrastructure HIV/AIDS epidemic Immigration from countries where TB is common Transmission of TB in congregate settings

18. Factors Contributing to the Decrease in TB Morbidity Since 1993 Increased efforts to strengthen TB control programs that Promptly identify persons with TB Initiate appropriate treatment Ensure completion of therapy

19. Reported Cases of TB by Country of Birth - United States, 1986-1998 86 8788899091929394959697 98 0 5 10 15 20 25 30 35 40 U.S.-born All Cases Foreign-born Recent Cases per 100,000 population Year

20. Resistance to INH $ 4% in 46 states and District of Columbia (DC) during 1993-1998 45 states and DC reported at least one MDR TB case during 1993-1998 Multidrug-Resistant TB (MDR TB) Remains a Serious Public Health Concern

21. MDR TB Cases, 1993 - 1998 None > 1 case

22. Persons at Higher Risk for Exposure to or Infection with TB Close contacts of person known or suspected to have TB Foreign-born persons from areas where TB is common Residents and employees of high-risk congregate settings Health care workers (HCWs) who serve high-risk clients

23. Persons at Higher Risk for Exposure to or Infection with TB (cont.) Medically underserved, low-income populations High-risk racial or ethnic minority populations Children exposed to adults in high-risk categories Persons who inject illicit drugs

24. Persons at Higher Risk of Developing TB Disease once Infected HIV infected Recently infected Persons with certain medical conditions Persons who inject illicit drugs History of inadequately treated TB

25. Testing for TB Disease and Infection

26. Purpose of Targeted Testing Find persons with LTBI who would benefit from treatment Find persons with TB disease who would benefit from treatment Groups that are not high risk for TB should not be tested routinely

27. All testing activities should be accompanied by a plan for follow-up care.

28. Groups That Should Be Tested for LTBI Persons at higher risk for exposure to or infection with TB Close contacts of a person known or suspected to have TB Foreign-born persons from areas where TB is common Residents and employees of high-risk congregate settings Health care workers (HCWs) who serve high- risk clients

29. Groups That Should Be Tested for LTBI (cont.) Persons at higher risk for exposure to or infection with TB Medically underserved, low-income populations High-risk racial or ethnic minority populations Children exposed to adults in high-risk categories Persons who inject illicit drugs

30. Groups That Should Be Tested for LTBI (Cont.) Persons at higher risk for TB disease once infected Persons with HIV infection Persons recently infected with M. tuberculosis Persons with certain medical conditions Persons who inject illicit drugs Persons with a history of inadequately treated TB

31. Administering the Tuberculin Skin Test Inject intradermally 0.1 ml of 5 TU PPD tuberculin Produce wheal 6 mm to 10 mm in diameter Do not recap, bend, or break needles, or remove needles from syringes Follow universal precautions for infection control

32. Reading the Tuberculin Skin Test Read reaction 48-72 hours after injection Measure only induration Record reaction in millimeters

33. Classifying the Tuberculin Reaction $ 5 mm is classified as positive in HIV-positive persons Recent contacts of TB case Persons with fibrotic changes on chest radiograph consistent with old healed TB Patients with organ transplants and other immunosuppressed patients

34. Classifying the Tuberculin Reaction (cont.) $ 10 mm is classified as positive in Recent arrivals from high-prevalence countries Injection drug users Residents and employees of high-risk congregate settings Mycobacteriology laboratory personnel Persons with clinical conditions that place them at high risk Children <4 years of age, or children and adolescents exposed to adults in high-risk categories

35. Classifying the Tuberculin Reaction (cont.) $ 15 mm is classified as positive in Persons with no known risk factors for TB Targeted skin testing programs should only be conducted among high-risk groups

36. Occupational Exposure to TB, Appropriate Cutoff Depends on Individual risk factors for TB Prevalence of TB in the facility

37. Factors that May Affect the Skin Test Reaction Type of Reaction Possible Cause False-positive Nontuberculous mycobacteria BCG vaccination Anergy False-negative Recent TB infection Very young age (< 6 months old) Live-virus vaccination Overwhelming TB disease

38. Anergy Do not rule out diagnosis based on negative skin test result Consider anergy in persons with no reaction if - HIV infected - Overwhelming TB disease - Severe or febrile illness - Viral infections - Live-virus vaccinations - Immunosuppressive therapy. Anergy skin testing no longer routinely recommended

39. Boosting Some people with LTBI may have negative skin test reaction when tested years after infection Initial skin test may stimulate (boost) ability to react to tuberculin Positive reactions to subsequent tests may be misinterpreted as a new infection

40. Two-Step Testing Use two-step testing for initial skin testing of adults who will be retested periodically If first test positive, consider the person infected If first test negative, give second test 1-3 weeks later If second test positive, consider person infected If second test negative, consider person uninfected

41. Diagnosis of TB

42. Evaluation for TB Medical history Physical examination Mantoux tuberculin skin test Chest radiograph Bacteriologic or histologic exam

43. Symptoms of Pulmonary TB Productive, prolonged cough (duration of $ 3 weeks) Chest pain Hemoptysis

44. Systemic Symptoms of TB Fever Chills Night sweats Appetite loss Weight loss Easy fatigability

45. Medical History Symptoms of disease History of TB exposure, infection, or disease Past TB treatment Demographic risk factors for TB Medical conditions that increase risk for TB disease

46. Mantoux Tuberculin Skin Test Preferred method of testing for TB infection in adults and children Tuberculin skin testing useful for - Examining person who is not ill but may be infected - Determining how many people in group are infected - Examining person who has symptoms of TB

47. Chest Radiograph Abnormalities often seen in apical or posterior segments of upper lobe or superior segments of lower lobe May have unusual appearance in HIV-positive persons Cannot confirm diagnosis of TB Arrow points to cavity in patient's right upper lobe.

48. Specimen Collection Obtain 3 sputum specimens for smear examination and culture Persons unable to cough up sputum, induce sputum, bronchoscopy or gastric aspiration Follow infection control precautions during specimen collection

49. Smear Examination Strongly consider TB in patients with smears containing acid-fast bacilli (AFB) Results should be available within 24 hours of specimen collection Presumptive diagnosis of TB

50. AFB smear AFB (shown in red) are tubercle bacilli

51. Cultures Use to confirm diagnosis of TB Culture all specimens, even if smear negative Results in 4 to 14 days when liquid medium systems used Colonies of M. tuberculosis growing on media

52. Drug Susceptibility Testing Drug susceptibility testing on initial M. tuberculosis isolate Repeat for patients who - Do not respond to therapy - Have positive cultures despite 2 months of therapy Promptly forward results to the health department

53. Persons at Increased Risk for Drug Resistance History of treatment with TB drugs Contacts of persons with drug-resistant TB Foreign-born persons from high prevalent drug resistant areas Smears or cultures remain positive despite 2 months of TB treatment Received inadequate treatment regimens for >2 weeks

54. Treatment of Latent TB Infection (LTBI)

55. Candidates for Treatment of LTBI Positive skin test result $5 mm HIV-positive persons Recent contacts of a TB case Persons with fibrotic changes on chest radiograph consistent with old TB Patients with organ transplants and other immunosuppressed patients

56. Candidates for Treatment of LTBI (cont.) Positive skin test result $10 mm Recent arrivals from high-prevalence countries Injection drug users Residents and employees of high-risk congregate settings Mycobacteriology laboratory personnel Persons with clinical conditions that make them high-risk Children < 4 years of age, or children and adolescents exposed to adults in high-risk categories

57. Candidates for Treatment of LTBI (cont.) Positive skin test result $ 15 mm Persons with no known risk factors for TB may be considered Targeted skin testing programs should only be conducted among high-risk groups

58. Treatment of LTBI with Isoniazid (INH) 9-month regimen considered optimal Children should receive 9 months of therapy Can be given twice-weekly if directly observed

59. Treatment of LTBI with a Rifamycin and Pyrazinamide (PZA) HIV-Positive Persons A rifamycin and PZA daily for 2 months May be given twice weekly Administration of rifampin (RIF) contraindicated with some protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) HIV-Negative Persons Clinical trials have not been conducted Daily RIF and PZA for 2 months May be given twice weekly

60. Contacts of INH-Resistant TB Treatment with a rifamycin and PZA If unable to tolerate PZA, 4-month regimen of daily RIF HIV-positive persons: 2 month regimen with a rifamycin and PZA Contacts of Multidrug-Resistant TB Use 2 drugs to which the infecting organism has demonstrated susceptibility Treat for 6 months or observe without treatment (HIV-negative) Treat HIV-positive persons for 12 months Follow for 2 years regardless of treatment

61. Fibrotic Lesions Acceptable regimens include 9 months of INH 2 months RIF plus PZA 4 months of RIF (with or without INH) Pregnancy and Breast-feeding INH daily or twice weekly Pyridoxine supplementation Breast-feeding not contraindicated

62. Monitoring Patients Before treatment for LTBI is started, clinicians should Rule out possibility of TB disease Determine history of treatment for LTBI or disease Determine contraindications to treatment Obtain information about current and previous drug therapy Recommend HIV testing if risk factors are present

63. Monitoring Patients (cont.) Establish rapport with patient and emphasize Benefits of treatment Importance of adherence to treatment regimen Possible adverse side effects of regimen Establishment of optimal follow-up plan

64. Monitoring Patients (cont.) Baseline laboratory testing Not routinely indicated Baseline hepatic measurements for - Patients whose initial evaluation suggests a liver disorder - Patients with HIV infection - Pregnant women and those in immediate postpartum period - Patients with history of chronic liver disorder

65. Monitoring Patients (cont.) At least monthly, evaluate for Adherence to prescribed regimen Signs and symptoms of active TB disease Signs and symptoms of hepatitis (if receiving isoniazid alone, and at 2, 4, and 8 weeks if receiving RIF and PZA)

66. Treatment of TB Disease

67. Basic Principles of Treatment Provide safest, most effective therapy in shortest time Multiple drugs to which the organisms are susceptible Never add single drug to failing regimen Ensure adherence to therapy

68. Adherence Nonadherence is a major problem in TB control Use case management and directly observed therapy (DOT) to ensure patients complete treatment

69. Case Management Assignment of responsibility Systematic regular review Plans to address barriers to adherence

70. Directly Observed Therapy (DOT) Health care worker watches patient swallow each dose of medication Consider DOT for all patients DOT should be used with all intermittent regimens DOT can lead to reductions in relapse and acquired drug resistance Use DOT with other measures to promote adherence

71. Treatment of TB for HIV-Negative Persons Include four drugs in initial regimen - Isoniazid (INH) - Rifampin (RIF) - Pyrazinamide (PZA) - Ethambutol (EMB) or streptomycin (SM) Adjust regimen when drug susceptibility results are known

72. Treatment of TB for HIV-Positive Persons Management of HIV-related TB is complex Care for HIV-related TB should be provided by or in consultation with experts in management of both HIV and TB

73. Treatment of TB for HIV-Positive Persons (cont.) RIF-based regimens generally recommended for persons Who have not started antiretroviral therapy For whom PIs or NNRTIs are not recommended Initial treatment phase should consist of Isoniazid (INH) Rifampin (RIF) Pyrazinzamide (PZA) Ethambutol (EMB) RIF may be used with some Pls and NNRTIs

74. Treatment of TB for HIV-Positive Persons (cont.) For patients receiving PIs or NNRTIs, initial treatment phase may consist of - Isoniazid (INH) - Rifabutin (RFB) - Pyrazinamide (PZA) - Ethambutol (EMB) An alternative nonrifamycin regimen includes INH, EMB, PZA, and streptomycin (SM)

75. Extrapulmonary TB In most cases, treat with same regimens used for pulmonary TB Bone and Joint TB, Miliary TB, or TB Meningitis in Children Treat for a minimum of 12 months

76. Pregnant women 9-month regimen of INH, RIF, and EMB PZA and SM are contraindicated PZA not contraindicated in HIV-positive pregnant women In most cases, treat with same regimens used for adults Treat as soon as diagnosis suspected Children Infants

77. Treatment Regimens for TB Resistant Only to INH HIV-Negative Persons Carefully supervise and manage treatment to avoid development of MDR TB Discontinue INH and continue RIF, PZA, and EMB or SM for the entire 6 months Or, treat with RIF and EMB for 12 months HIV-Positive Persons Regimen should consist of a rifamycin, PZA, and EMB

78. Multidrug-Resistant TB (MDR TB) Presents difficult treatment problems Treatment must be individualized Clinicians unfamiliar with treatment of MDR TB should seek expert consultation Always use DOT to ensure adherence

79. Monitoring for Adverse Reactions Baseline measurements Monitor patients at least monthly Monitoring for adverse reactions must be individualized Instruct patients to immediately report adverse reactions

80. Monitoring Response to Treatment Monitor patients bacteriologically monthly until cultures convert to negative After 3 months of therapy, if cultures are positive or symptoms do not resolve, reevaluate for - Potential drug-resistant disease - Nonadherence to drug regimen If cultures do not convert to negative despite 3 months of therapy, consider initiating DOT

81. Infection Control in Health Care Settings

82. Infectiousness Patients should be considered infectious if they Are coughing Are undergoing cough-inducing or aerosol-generating procedures, or Have sputum smears positive for acid-fast bacilli and they Are not receiving therapy Have just started therapy, or Have poor clinical response to therapy

83. Infectiousness (cont.) Patients no longer considered infectious if they meet all of these criteria: Are on adequate therapy Have had a significant clinical response to therapy, and Have had 3 consecutive negative sputum smear results

84. Infection Control Measures Administrative controls to reduce risk of exposure Engineering controls to prevent spread and reduce concentration of droplet nuclei Personal respiratory protection in areas where increased risk of exposure

85. Administrative Controls Reduce risk of exposing uninfected persons to infectious disease: Develop and implement written policies and protocols to ensure - Rapid identification - Isolation - Diagnostic evaluation - Treatment Implement effective work practices among HCWs Educate, train, and counsel HCWs about TB Test HCWs for TB infection and disease

86. Administrative Controls (cont.) Perform risk assessment and classification of facility based on Profile of TB in community Number of infectious TB patients admitted Analysis of HCW skin test conversions

87. Engineering Controls To prevent spread and reduce concentration of infectious droplet nuclei Use ventilation systems in TB isolation rooms Use HEPA filtration and ultraviolet irradiation with other infection control measures

88. Personal Respiratory Protection Use in areas where increased risk of exposure: TB isolation rooms Rooms where cough-inducing procedures are done Homes of infectious TB patients

89. BCG Vaccination

90. Recommendations for BCG Vaccination Not recommended in immunization programs or TB control programs in the U.S. BCG vaccination undertaken after consultation with health department

91. Considered for an infant or child with negative skin-test result who Is continually exposed to untreated or ineffectively treated patient Will be continually exposed to multidrug-resistant TB Recommendations for BCG Vaccination (cont.)

92. Recommendations for BCG Vaccination (cont.) HCWs considered on individual basis in settings in which High percentage of MDR TB patients has been found Transmission of drug-resistant TB strains and subsequent infection are likely, and Comprehensive TB infection-control precautions implemented and not successful

93. BCG Contraindications Contraindicated in persons with impaired immune response from HIV infection Congenital immunodeficiency Leukemia Lymphoma Generalized malignancy Receiving high-dose steroid therapy Receiving alkylating agents Receiving antimetabolites Receiving radiation therapy

94. BCG Vaccination and Tuberculin Skin Testing Tuberculin skin testing not contraindicated for BCG-vaccinated persons LTBI diagnosis and treatment for LTBI considered for any BCG- vaccinated person whose skin test reaction is $ 10 mm, if any of these circumstances are present: - Was contact of another person with infectious TB - Was born or has resided in a high TB prevalence country - Is continually exposed to populations where TB prevalence is high

95. Community TB Control

96. Preventing and Controlling TB Three priority strategies: Identify and treat all persons with TB disease Identify contacts to persons with infectious TB; evaluate and offer therapy Test high-risk groups for LTBI; offer therapy as appropriate

97. Health care providers should work with health department in the following areas: Overall planning and policy development Identification of persons with clinically active TB Management of persons with disease or TB suspects Identification and management of persons with LTBI Laboratory and diagnostic services Data collection and analysis Training and education

98. Overall Planning and Policy Develop overall TB control strategy Review local laws, regulations, and policies Guide and oversee TB control efforts of local institutions and practitioners Provide consultations in TB treatment, contact investigations, and infection control practices Seek out necessary funding and resources Educate policymakers

99. Identification of Persons Who Have Clinically Active TB •Health department has ultimate responsibility for ensuring TB patients do not transmit TB Contact Investigation Purpose of a contact investigation is to find persons who Have TB disease so treatment can be given, and further transmission stopped Have LTBI so treatment can be given Are at high risk of developing TB disease and require treatment until LTBI excluded

100. Management of Persons Who Have TB Disease or TB Suspects Management involves range of services, which include •Developing a treatment plan •Promoting and ensuring adherence •Providing a referral system for other medical problems •Providing clinical consultation services •Providing inpatient care when necessary •Providing appropriate facilities to isolate and treat patients with infectious TB •Maintaining an infection control program

101. Identification and Management of Persons with LTBI Establish working relationships with other health care providers Target testing to well-defined high-risk groups Flexibility needed in defining high-priority groups

102. Laboratory and Diagnostic Services Readily accessible AFB results within 24 hours of specimen collection Clinicians promptly report all TB cases and suspected cases All TB smear and culture results reported by laboratories

103. Data Collection and Analysis TB reporting required in every state All new cases and suspected cases promptly reported to health department All drug susceptibility results sent to health department

104. Training and Education TB control programs should Provide training for program staff Provide leadership in TB education to the community Ensure community leaders, clinicians, and policymakers are knowledgeable about TB Educate the public